Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

Future Med Chem. 2012 Feb;4(2):163-75. doi: 10.4155/fmc.11.181.

Abstract

One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Butyrylcholinesterase / genetics
  • Carboxylic Ester Hydrolases / genetics
  • Cocaine / metabolism*
  • Cocaine / toxicity
  • Cocaine-Related Disorders / enzymology
  • Cocaine-Related Disorders / therapy*
  • Humans
  • Mutation

Substances

  • Carboxylic Ester Hydrolases
  • cocaine esterase
  • Butyrylcholinesterase
  • Cocaine